HIV/AIDS afflicts nearly 37 million people worldwide. At present there is no cure or vaccine. New antivirals must be developed to combat drug resistance, while addressing the needs of an aging population requiring decades of therapy compliance. Existing FDA-approved drugs target many facets of the viral life cycle. To improve long-term therapeutic outcome, modulation of new targets—especially those resistant to mutation—is needed.
The HIV-1 Trans-Activation Responsive element (TAR) is highly resistant to mutation and plays important roles in facilitating proviral transcription and blocking apoptosis of the infected host cell. Despite its central importance in the HIV life cycle, TAR has been refractory to the discovery of small-molecules or peptides with sufficient affinity and selectivity to warrant pharmaceutical development. Crawford et al. described 70 different proteins, referred to as TAR binding proteins (TBPs), that specifically recognize TAR through combined interactions of the N- and C-terminal helix present in each TBP (Crawford et al. ACS Chem Biol, 2016, 11(8): 2206-2215). However, due to the size of these proteins, pharmaceutical development is not ideal.
Thus, there remains a need in the art for new HIV therapeutics.